DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/01/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of the Claims
Claims 1-19, 21, and 32-33 are pending in this application. Claims 20, 22-31, and 34-35 have been cancelled by Applicant.
Claim Objections
Claims 4-5 and 17-18 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Interpretation
The specification broadly defines the term "C2-6alkynyl" as a monovalent linear or branched hydrocarbon group of 2 to 6 carbon atoms with at least one triple bond. "haloC3-6alkynyl" is broadly defined as a C3-6alkynyl group wherein at least one of the hydrogen atoms of the C3-6alkynyl group have been replaced by same or different halogen atoms.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-3, 6-16, 21, and 32-33 are rejected under 35 U.S.C. 103 as being unpatentable over Corcoran et al. (WO 2022/21894 A1 – Int. Filing Date: 01/04/2022 – cited in IDS) (“Corcoran”); in view of Meanwell et al. (J. Med. Chem. 2011, 54, 2529–2591) (“Meanwell”).
Regarding claims 1-2 and 6-15, Corcoran discloses their compounds as an inhibitor of RAS proteins for the treatment for cancer – which is the same intended use as the instant invention (see pages 1-2). Corcoran discloses the compounds of Formula AI-i below, wherein A (corresponding to instant A1) can be
PNG
media_image1.png
90
146
media_image1.png
Greyscale
; R7-8 (corresponding to instant A2) can be alkyl; B may be absent or may be alkyl; L is absent or a linker, such as
PNG
media_image2.png
96
123
media_image2.png
Greyscale
, wherein Xb is -C(O)-, Cy is cycloalkyl or heterocycle (all reading on instant R1 being
PNG
media_image3.png
93
98
media_image3.png
Greyscale
and R9 being cycloalkyl or acetidinyl), L3 can be absent or -C(O)-. Corcoran discloses specifically their linker may be
PNG
media_image4.png
66
100
media_image4.png
Greyscale
(reading on R9 being acetidinyl),
PNG
media_image5.png
62
115
media_image5.png
Greyscale
(see page 300 – reading on R9 being C3-cycloalkyl), or
PNG
media_image6.png
76
117
media_image6.png
Greyscale
(reading on R9 being phenyl) etc.; W can be H,
PNG
media_image7.png
81
90
media_image7.png
Greyscale
, or
PNG
media_image8.png
91
103
media_image8.png
Greyscale
(page 305 – reading on R9 substituted with haloalkynyl groups); R2 (corresponding to instant R5) can be alkyl; the group corresponding to instant R6 is an alkoxyalkyl; and the group corresponding to instant R7 is an alkyl-piperazineyl (see pages 53-63).
PNG
media_image9.png
502
546
media_image9.png
Greyscale
Corcoran discloses their preferred embodiment AA465 below (page 182), for example, which reads on the instant compounds when instant R2 is isopropyl, R5 is ethyl, R6 is 1-methoxyethyl, R7 is 4-methylpiperazin-1yl, A2 is dimethylmethylene, and R1 is
PNG
media_image10.png
100
96
media_image10.png
Greyscale
, wherein R8 is methyl, and R9 is azetidinyl. While Corcoran’s preferred embodiment below does not show their group corresponding to instant R9 being azetidinyl substituted by a haloC3-6alkynyl, Corcoran specifically teaches their W group (corresponding to a substituent on their linker L, which corresponds to instant R1-R9) can be, for example,
PNG
media_image11.png
90
105
media_image11.png
Greyscale
(see page 305) – reading on R9 being azetidinyl substituted by a haloC3-6alkynyl (see claim interpretation). Thus, Corcoran discloses a broad genus, which reads on the claimed subgenus.
PNG
media_image12.png
302
563
media_image12.png
Greyscale
While in Corcoran’s compounds both positions corresponding to instant R3-4 are always H; the teachings of Meanwell are relied upon to leverage these differences.
Meanwell teaches that the design of bioisosteres frequently introduces structural changes that can be beneficial depending on the context, with size, shape, electronic distribution, polarizability, dipole, polarity, lipophilicity, and pKa potentially playing key contributing roles in molecular recognition and mimicry. In the contemporary practice of medicinal chemistry, the development and application of bioisosteres have been adopted as a fundamental tactical approach useful to address a number of aspects associated with the design and development of drug candidates (abstract). Meanwell teaches H and F as classical monovalent bioisosteres (Table 1, page 2530, col. 1).
Therefore, regarding claims 1-2 and 6-15, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by Corcoran’s disclosed formulae and preferred embodiments, in view of Meanwell; In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). See MPEP 2144.08. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of RAS protein inhibitors for the treatment of cancers disclosed by Corcoran; in view of Meanwell’s teachings that H and F are classical bioisosteres, and changing one for the other may result in beneficial properties of lead compounds. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, including those encompassed by the claims, by replacing the oxetane corresponding to Corcoran’s W in AA465 with the halo-alkynyl group shown above, for example, and substituting a H corresponding to instant R3 or R4 with F, in view of Meanwell, to arrive at the instant claims.
Further regarding claim 2, with respect to stereoisomerism, it is noted that in Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293 (Fed. Cir. 2007), the court also relied on the settled principle that in chemical cases, structural similarity can provide the necessary reason to modify prior art teachings. The Federal Circuit also addressed the kind of teaching that would be sufficient in the absence of an explicitly stated prior art-based motivation, explaining that an expectation of similar properties in light of the prior art can be sufficient, even without an explicit teaching that the compound will have a particular utility. The Federal Circuit cautioned that requiring such a clearly stated motivation in the prior art to isolate 5(S) ramipril ran counter to the Supreme Court' s decision in KSR. The court stated: [r]equiring an explicit teaching to purify the 5(S)-stereoisomer from a mixture in which it is the active ingredient is precisely the sort of rigid application of the TSM test that was criticized in KSR. Id. at 1301 (See MPEP 2143).
Regarding claims 3 and 16, Corcoran discloses their linker may be
PNG
media_image2.png
96
123
media_image2.png
Greyscale
wherein Xb is -C(O)-, Cy can be cycloalkyl, L3 can be absent or -C(O)-, and the linker may be
PNG
media_image5.png
62
115
media_image5.png
Greyscale
(reading on R1 being
PNG
media_image10.png
100
96
media_image10.png
Greyscale
, wherein R8 is methyl, and R9 is cyclopropyl) bound to Corcoran’s W group, which may be
PNG
media_image11.png
90
105
media_image11.png
Greyscale
(for example – reading on instant R9 being substituted by haloalkyl).
Regarding claim 21, Corcoran discloses pharmaceutical compositions comprising their compounds and pharmaceutical excipients (pages 524, 670, and 882, etc.).
Regarding claim 32, Corcoran discloses their compounds in methods for the treatment of cancers, including colorectal cancer, etc. (page 888). Regarding claim 33, Corcoran discloses their compounds in the treatment of cancers with RAS mutations such as G12C and A59T and several others, and combinations thereof (page 889). Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer Corcoran’s compounds of the treatment of cancers with KRAS mutations in G12C and A59T. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Corcoran’s disclosure.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Corcoran et al. (WO 2022/21894 A1 – Int. Filing Date: 01/04/2022 – cited in IDS) (“Corcoran”); in view of Meanwell et al. (J. Med. Chem. 2011, 54, 2529–2591) (“Meanwell”); as applied to claims 1-3, 6-16, 21, and 32-33; further in view of Aay et al. (WO 2022/060836 A1 – Int. Filing Date: 09/15/2021 – Cited in IDS) (“Aay”).
The teachings of Corcoran and Meanwell are disclosed above and incorporated herein.
Corcoran further discloses their compounds being synthesized via a routine amide coupling conditions which one of ordinary skill in the art would be able to determine – see, for example, Scheme C3, page 679:
PNG
media_image13.png
233
867
media_image13.png
Greyscale
While Corcoran doesn’t specifically disclose their amide coupling conditions, the teachings of Aay are relied upon for these disclosures.
Aay discloses a related amide coupling reaction using HATU and DIEA (same as instantly claimed DIPEA – see definitions on page 283) as base (see Example A14, page 301, for example):
PNG
media_image14.png
200
658
media_image14.png
Greyscale
Therefore, regarding claim 19, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to prepare the instant compounds, as described above, and as taught by Corcoran in view of Meanwell, further in view of Aay. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Corcoran in view of Meanwell disclose the claimed compounds and Corcoran states their compounds can be prepared using amide coupling reagents; further because Aay discloses a similar amide coupling conditions with HATU and DIPEA.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
Examiner interviews are available via telephone and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney L. Klinkel can be reached at (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
Prosecution Insights